Essential Medicines List For Children Research Articles

Evaluation of alignment of the reimbursement medicines list for children in Albania with the WHO essential medicines list for children.

The WHO Essential Medicine List for Children was released on the 30th anniversary of the general Essential Medicine List in 2007, to recognise special needs for medicines in children, and to promote the inclusion of paediatric medicines in national procurement programmes. This study aimed to investigate the alignment of the medicines included in the Albanian reimbursement medicines list of the Mandatory Healthcare Insurance Fund (AMHIF) and the Essential Medicine List for Children. A quantitative evaluation was performed to compare the paediatric medicines included in the 2022 list of the AMHIF and the 2021 WHO Essential Medicine List for Children. In addition, vaccines in the Albanian vaccination programmes for children were compared to the ones listed on the WHO Essential Medicine List for Children. Both lists had a total of 284 active ingredients in common, whereas 14 of 24 vaccines were found to be in common in the Essential Medicine List for Children list and the Albanian vaccination programmes. This is the first study in Albania to investigate the alignment of the WHO EMLc and AMHIF list. In case of the same active ingredient there were many deviations in terms of dosage form, strength and indication.

Alignment in the registration, selection, procurement and reimbursement of essential medicines for childhood cancers in South Africa

IntroductionThe effectiveness of a health system in providing access to medicines is in part determined by the alignment of several core pharmaceutical processes. For South Africa’s public health sector, these...

WHO O2CoV2: oxygen requirements and respiratory support in patients with COVID-19 in low-and-middle income countries—protocol for a multicountry, prospective, observational cohort study

IntroductionSARS-CoV-2 has been identified as the cause of the disease officially named COVID-19, primarily a respiratory illness. COVID-19 was characterised as a pandemic on 11 March 2020. It has been...

Variations in global prices of chemotherapy for childhood cancer: a descriptive analysis.

The stark disparity in survival for children with cancer across the world has inspired a global call to expand chemotherapy access in low and middle income countries. Among the numerous barriers to success, a paucity of reliable information regarding chemotherapy pricing hinders the ability of governments and other key stakeholders to make informed budget decisions or negotiate lower medication prices. The aim of this study was to generate comparative price information on both individual chemotherapy agents and comprehensive treatment regimens for common childhood cancers using real-world data. Chemotherapy agents were selected based on their inclusion in the World Health Organization (WHO) Essential Medicines List for Children (EMLc) and their use in frontline regimens for the tracer cancer types prioritized by the WHO's Global Initiative for Childhood Cancer (GICC). Sources included IQVIA MIDAS data, obtained under license from IQVIA, and publicly available data from Management Sciences for Health (MSH). Data on chemotherapy prices and purchase volumes spanning 2012-2019 were aggregated according to WHO region and World Bank (WB) income classification. Cumulative chemotherapy prices for treatment regimens were compared across WB income classification. Data representing an estimated 1.1 billion doses of chemotherapy were obtained for 97 countries: 43 high income countries (HICs), 28 upper middle income countries (UMICs), and 26 low and lower middle income countries (LLMICs). Median drug prices in HICs were 0.9-20.4 times those of UMICs and 0.9-15.5 times those of LMICs. Regimen prices were generally higher for HICs, hematologic malignancies, non-adapted protocols, and higher risk stratification or stage, albeit with notable exceptions. This study represents the largest price analysis to date of chemotherapy agents used globally in childhood cancer therapy. The findings of this study form a basis for future cost-effectiveness analysis in pediatric cancer and should inform efforts of governments and stakeholders to negotiate drug prices and develop pooled purchasing strategies. NB received funding support from the American Lebanese Syrian Associated Charities and Cancer Center Support grant (CA21765) from the National Cancer Institute through the National Institutes of Health. TA received funding through the University of North Carolina Oncology K12 (K12CA120780) and the University Cancer Research Fund from the UNC Lineberger Comprehensive Cancer Center.

Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE.

Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology (SIOPE) Essential Anticancer Medicines Project was to provide a list of anticancer medicines that are considered essential in the treatment of paediatric cancers to help ensure their continuous access to all children and adolescents with cancer across Europe. This pan-European project, done between Jan 20, 2020, and Feb 18, 2022, was designed to be a systematic collection and review of treatment protocols and strategies that are used to treat childhood cancer in Europe. We formed 16 working groups on the basis of paediatric cancer types, and which were based on the existing SIOPE Clinical Trial Groups. Workings groups consisted of representatives from the SIOPE Clinical Trial Groups, Young SIOPE members, and senior paediatric oncology experts. Each group collected existing treatment protocols that are used to treat the respective cancer types in Europe. Medicines from the standard group of each protocol were extracted. For medicines not on the WHO Essential Medicines List for children (EMLc) 2017, working groups did a literature search to determine whether the medicines should be defined as essential, promising, or neither essential nor promising. Each group provided an individual summary, and all medicines that were considered essential by at least one group were combined in a joint list. The working groups identified 73 treatment protocols used in Europe and defined 66 medicines as essential. For several newer medicines, such as kinase inhibitors or tisagenlecleucel, the supporting evidence was insufficient to consider them essential, so these medicines were defined as promising. 25 medicines were considered promising by at least one working group. 22 (33%) of the 66 essential and none of the promising medicines were included in the WHO EMLc 2017. The WHO EMLc 2021 included two new medicines (everolimus and vinorelbine) following applications we made as a result of this project. Medicines that were defined as essential within this project should be available for the treatment of childhood and adolescent cancer continuously and across Europe. This list can be used to support and guide stakeholders and policy makers in negotiations on a national and European level regarding shortages, accessibility, and affordability of these medicines. None.

Determinants of access to childhood cancer medicines: a comparative, mixed-methods analysis of four Caribbean countries

Equitable access to essential medicines is a key facet of childhood cancer care, recognised by WHO as vital to improved childhood cancer outcomes globally. In the Caribbean, childhood cancer outcomes are poorer than those in most high-income countries. We aimed to generate in-depth comparative evidence of the current challenges and opportunities related to access to childhood cancer medicines in the Caribbean to identify context-sensitive health systems strategies to improve drug access and inform evidence-based paediatric cancer policies in the region. In this convergent, parallel, mixed-methods study, we mapped and analysed the determinants of access to childhood cancer medicines in four Caribbean countries (The Bahamas, Barbados, Jamaica, and Trinidad and Tobago). We analysed contextual determinants of access to medicines within and across study site jurisdictions, alignment of childhood cancer medicine inclusion between each country's national essential medicines list (NEML) and WHO's 2017 Essential Medicines List for Children, and availability and cost of chemotherapeutic agents at five tertiary care hospitals. We used a mixed-effects logistic regression model to analyse the association of medicine price, procurement efficiency (via median price ratio [MPR]), and site with drug availability. The fixed effect evaluated the effect of site and MPR on the probability of stockout in a given month. We assessed determinants of medicine access via thematic analysis of semi-structured qualitative interviews, literature, and policy documents. We collected and analysed data for 28 childhood cancer medicines from Barbados, 32 from The Bahamas, 30 from Trinidad and Tobago, and 31 from Jamaica. Despite stepwise inclusion of childhood cancer medicines in NEMLs, all four countries had frequent and recurrent stockouts for many cytotoxic medicines, showing no consistent relationship between NEML inclusion and availability. A mean MPR of greater than 3·0 in Trinidad and Tobago, The Bahamas, and Barbados suggests uniformly high procurement inefficiency, resulting in significant effects on drug stockout days. For each one unit increase in MPR the adjusted odds ratio (OR) of stockout increased by 10% (adjusted OR 1·10, 95% CI 1·04-1·16; p<0·01). These challenges in access to childhood cancer medicines stem from health system and policy dynamics at institutional, national, and supranational levels that cause price volatility and erratic medicine availability. Key challenges include disparate policy commitments (eg, among sites), inefficient procurement and supply chain management practices, and local effects of international market pressures. The Caribbean region exemplifies deficiencies in access to childhood cancer medicines that might be overcome by improved regional harmonisation of drug registration, pharmacovigilance, and procurement alongside national forecasting to strengthen global pharmaceutical planning and prioritisation. Focused political attention to address these challenges is required to ensure efficient, reliable, and sustained availability of cancer mediciness. The SickKids-Caribbean Initiative.

3D printing of drugs: expanding the options for child-tailored pharmacotherapy

Lack of age-appropriate commercially available drugs hinders adequate pharmacotherapy in children. The European Union Paediatric Regulation (EC No1901/2006) and the establishment of the EU Paediatric Committee PDCO (2007) were aimed...

Should Codeine Still be Considered a WHO Essential Medicine?

Codeine continues to be widely used as an analgesic, antidiarrhoeal and antitussive agent. Its analgesic effect depends on its biotransformation to morphine, a strong opioid. The highly variable biotransformation of codeine to morphine, catalysed by CYP2D6, underlies the pronounced interindividual variability of its analgesic response. Randomized controlled trials have demonstrated that codeine administered alone has the poorest analgesic effect among all commonly used analgesics in acute postoperative pain. Moreover, it is highly unlikely that the low dose of codeine contributes to the pain-relieving effect of the non-opioid component in combination analgesic products. In addition, there is a lack of reliable clinical evidence to support the use of codeine as an antitussive in acute or chronic cough. Codeine use, through its active metabolite morphine, has the potential to lead to abuse and dependence. The World Health Organization (WHO) removed codeine from the essential medicines list for children in 2011. Based on the available information in the scientific literature on the efficacy and safety of codeine, the WHO should seriously consider removing it also from the list of essential medicines for adults, which would be a strong signal for all health professionals to prescribe and dispense codeine with the utmost caution.

Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations.

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI −55.7%, +29.9%) at 8°C and 72.3% (95% CI −82.8%, −61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI −51.9%, +21.2%) at 23 °C and 21.7% (−28.2%, −15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children.

What are the volume and budget needs to provide chemotherapy to all children with acute lymphoblastic leukaemia in Thailand? Development and application of an estimation tool

ObjectiveInsufficient access to anticancer medicines may contribute to the wide survival differences of children with cancers across the globe. We developed a tool to estimate the volume of medicines and...

Availability of Authorizations from EMA and FDA for Age-Appropriate Medicines Contained in the WHO Essential Medicines List for Children 2019.

Lack of age-appropriate commercially drug products availability is a common problem in pediatric therapeutics; this population needs improved and safer drug delivery. In addition, biopharmaceutic aspects, dosage requirements, and swallowing abilities demand pediatric forms different to adult formulations. The objective of this study was to evaluate the authorization availability from United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) of oral essential medicines for children and analyze its age-appropriateness for oral administration in children. All oral drugs from 7th List of Essential Medicines for Children by World Health Organization (WHO) were selected. Availability of commercial drug products was collected from OrangeBook, Spanish drug product catalogue, British electronic Medicines Compendium, and the International Vademecum. Tablets, effervescent tablets, and capsules were considered as not age-appropriate forms. Liquid forms, powder for oral suspension, mini tablets, granules, and soluble films were considered as age-appropriate forms due to their flexibility. More than 80% of the studied drugs possess a commercial authorization in oral forms in both EMA and FDA. Nevertheless, around 50% of these formulations are not age-appropriate for most pediatric groups. This study shows the lack of age-appropriate medicines for children. More efforts are needed to improve development and approval of pediatric medicines.

Access to WHO Essential Medicines for Childhood Cancer Care in Trinidad and Tobago: A Health System Analysis of Barriers and Enablers.

PURPOSEImproving access to essential medicines is necessary to reduce global mortality resulting from childhood cancer. However, there is a lack of context-specific data in many low- to middle-income countries on the determinants of access to essential childhood cancer medicines. We conducted a mixed-methods case study of the barriers to and enablers of access to WHO essential medicines for childhood cancer care in Trinidad and Tobago, in response to domestic calls for policy attention and reform.METHODSWe interviewed stakeholders (N = 9) across the pharmaceutical supply system using a novel analytic framework and qualitative interview guide. Interviews were recorded, transcribed, and analyzed with constant comparative methods to capture emergent themes. Quantitatively, we examined alignment of the national essential medicines list with the 2017 WHO Essential Medicines List for Children (EMLc). National buyer prices for EMLc cancer medicines were compared with median international prices, with calculation of median price ratios to assess procurement efficiency.RESULTSPrincipal barriers identified included a lack of data-driven procurement, low supplier incentive to engage in tenders, reactive rather than proactive processes in response to stockouts, and siloed information systems. Recurring themes of regionalization, standardization, and proactivity emerged as priorities for policy reform. Quantitative analysis of the national essential medicines list and median price ratios for procured medicines aligned with findings reported qualitatively.CONCLUSIONOur study contributes to global efforts to improve childhood cancer care by identifying policy-relevant evidence on access to essential childhood cancer medicines and providing a model for future studies in other jurisdictions.

Access to essential cardiovascular medicines for children: a pilot study of availability, price and affordability in Nigeria.

Policies to improve access to medicines for children in low- and middle-income countries, such as Nigeria, should consider the growing threat of non-communicable diseases. The aim of this pilot study was to scope availability, price and affordability of essential cardiovascular medicines for children in selected states in Nigeria. The study was a descriptive longitudinal survey conducted in three phases. Availability was determined as percentage of facilities having the medicine on the survey date. Medicines with good availability (>80%) were noted. Prices were cross-referenced against international Reference Prices and the Nigerian National Health Insurance Scheme Prices. Affordability was calculated using the Least-Paid Government Worker method. For medicines compounded to improve availability, a model for calculating affordability was proposed. In Phase I, the availability of all 17 strengths of the cardiovascular medicines or diuretics listed in the Essential Medicines List for Children (2015) were surveyed in two conveniently selected states using the WHO/HAI questionnaire. Data were collected from 17 hospitals and pharmacies. Phases II and III focused on tablet formulations (enalapril, furosemide, hydrochlorothiazide and spironolactone) in three purposively selected state capitals: Lagos, Abuja and Yenagoa. In Phase II, 11 private pharmacies were surveyed in December 2016: Phase III tracked price changes in Abuja and Yenagoa in August 2018. Only furosemide and hydrochlorothiazide tablets had good availability. Oral liquids were unavailable. Prices for four generic oral tablets were 2–16× higher than the International Reference Prices; prices for two of these did not change significantly over the study period. Affordable medicines were generic furosemide and hydrochlorothiazide tablet. Where a fee is charged, compounded medicines were also not affordable. While the small sample sizes limit generalization, this study provides indicative data suggesting that prices for cardiovascular medicines remain high and potentially unaffordable in the private sector in these selected states, and when compounded. Regular systematic access surveys are needed.

Classification of WHO Essential Oral Medicines for Children Applying a Provisional Pediatric Biopharmaceutics Classification System.

The objective was using the Essential Medicines List for children by the World Health Organization (WHO) to create a pediatric biopharmaceutics classification system (pBCS) of the oral drugs included in the Essential Medicines List by the World Health Organization and to compare our results with the BCS for adults (aBCS). Several methods to estimate the oral drug dose in different pediatric groups were used to calculate dose number (Do) and solubility (high/low). The estimation of the gastrointestinal water volume was adapted to each pediatric group. Provisional permeability classification was done by comparison of each drug lipophilicity versus metoprolol as the model drug of high permeability. As a result, 24.5% of the included drugs moved from the favorable to unfavorable class (i.e., from high to low solubility). Observed changes point out potential differences in product performance in pediatrics compared to adults, due to changes in the limiting factors for absorption. BCS Class Changes 1 to 2 or 3 to 4 are indicative of drugs that could be more sensitive to the choice of appropriate excipient in the development process. Validating a pBCS for each age group would provide a valuable tool to apply in specific pediatric formulation design by reducing time and costs and avoiding unnecessary pediatric experiments restricted due to ethical reasons. Additionally, pBCS could minimize the associated risks to the use of adult medicines or pharmaceutical compound formulations.

Estimating global trends in total and childhood antibiotic consumption, 2011-2015

IntroductionUnderstanding patterns of antibiotic consumption is essential to ensure access to appropriate antibiotics when needed and to minimise overuse, which can lead to antibiotic resistance. We aimed to describe changes...

Global Access to Essential Medicines for Childhood Cancer: A Cross-Sectional Survey.

PurposeGlobal data mapping access to essential chemotherapeutics for pediatric cancer are scarce. We report a survey of international pediatric cancer care providers’ access to these medicines.MethodsA Web-based survey was sent to pediatric oncologists registered on the Cure4Kids Web portal. We queried chemotherapeutics in the WHO Essential Medicines List for Children, from which the average proportional availability was summarized as each country’s access score. In addition, we examined availability of drug packages defined by the WHO-sanctioned Expert Committee for eight pediatric cancers. We undertook a sensitivity analysis investigating how regimen access would change if the cytotoxics specified in recent agreements between the Clinton Health Access Initiative, American Cancer Society, and pharmaceutical companies were universally available.ResultsThere were significant (P < .001) differences in the median access scores between World Bank income groups, and 42.9% of respondents from low-income and lower middle–income countries reported suboptimal access scores. Our disease-based analysis revealed that 42.1% of patients in low-income and lower middle–income countries lacked full access to chemotherapy packages. Guaranteed availability of the cytotoxics specified in the Clinton Health Access Initiative/American Cancer Society agreements was projected to increase this regimen-based access by 1.6%, although including four additional chemotherapeutics would further increase coverage by 13.9%.ConclusionThis study is the first, to our knowledge, to assess worldwide variation in practical access to pediatric chemotherapy. Although mapping the proportion of available chemotherapeutics is informative, we also developed a meaningful estimate of access using disease-specific drug packages. These data provide an important baseline for continued monitoring and can aid in planning adaptive treatment guidelines that consider the trade-offs between access and outcomes.

Availability, affordability and costs of pediatric medicines in Mongolia

BackgroundThe Essential Medicines List for Children (EMLc) was developed by the World Health Organization (WHO) to assist member countries to achieve Millennium Development Goals (MDG). The Government of Mongolia has adopted a National Essential Drug List (NEDL) with the seventh update published in 2014. The objective of this study was to determine the accessibility, availability and costs of essential pediatric medicines in Mongolia.MethodsA standardized methodology developed by the WHO and Health Action International (HAI) was employed to conduct a study on the availability, costs and affordability of pediatric medicines in Mongolia. A data collection tool collected information in regards to retail and wholesale availability and costs of essential pediatric medicines at pharmacy outlets during January and August of 2016.ResultsAvailability of individual essential pediatric medicines varied across the country. The average availability of medicines was 72.6% in the public sector (9.1–100%). Correspondingly, average availability of all selected medicines in the private sector was 76.7% (26.7–100%). Lowest price medicines were 2.45 times higher than the international reference price (IRP) in the private sector and was 1.95 times higher in the public sector. The lowest cost medicines in the public sector were more affordable for all conditions. The least affordable treatment was estimated to be for respiratory tract infections, or otitis media using amoxicillin clavulanic acid, suspension costing up to 1.03 days wages.ConclusionProcurement, supply and distribution of essential pediatric medicines needs to be regularly investigated in order to identify the availability and costs of pediatric formulations in Mongolia.

Development of a provisional essential medicines list for children in Canada: consensus process.

Worldwide, many countries have developed a list of essential medicines for children to improve prescribing. We aimed to create an essential medicines list for children in Canada. We adapted the previously created preliminary list of essential medicines for adults in Canada and the WHO Model List of Essential Medicines for Children to create a provisional list of essential medicines for children in Canada. Canadian clinicians made suggestions for changes. Literature relevant to each suggestion was presented to clinician-scientists, who used a modified nominal group technique to make recommendations on the suggestions. Ontario Public Drug Programs prescription data were reviewed to identify commonly prescribed medications missing from the list. Literature relevant to these medications was shared with a clinician-scientist review panel to determine which should be added, and a revised list was developed. A total of 76 items were removed from the list of essential medicines for adults in Canada because they were not indicated for use in children or were not relevant in the Canadian health care context; 7 medications were added to the child list based on Ontario Public Drugs Programs prescribing data and clinician-scientist review. Suggestions to add, remove or substitute medications were made by peer-reviewers and resulted in removal of 1 medication and replacement of 1 medication. The process produced a provisional list of 67 essential medications for children. A provisional list of 67 essential medicines for children was created through a peer-reviewed, multistep process based on current clinical evidence, Canadian clinical practice guidelines and historical prescribing data. It is publicly posted at http://cleanmeds.ca/. The list should be further developed based on wider input and should be continuously revised based on emerging evidence of the safety and effectiveness of these medicines in all pediatric age groups.

Are age-appropriate antibiotic formulations missing from the WHO list of essential medicines for children? A comparison study

ObjectiveThere is a global call for formulations, which are better suited for children of different age categories and in a variety of settings. One key public health area of interest...

Access to age-appropriate essential medicines: a retrospective survey of compounding of medicines for children in hospitals in Nigeria and implications for policy development.

Policies to improve access to medicines for children in Nigeria do not include compounding as a source of medicines. Compounding is often applied as a last resort in health institutions to provide age-appropriate formulations usually for oral use in young children; but it bears some risk. Some countries have adopted policies aimed at reducing the risk based on available data. There is not much data for Nigeria. This retrospective study examined compounding records from January to December 2011 in a sample of seven hospitals to describe what medicines for oral use were commonly compounded in Nigeria. It then determined if these medicines were commercially available in forms suitable for use in children in selected countries—the United Kingdom, United States and India. The study found that out of 2845 items compounded, over 65% were medicines for cardiovascular conditions, diarrhoea or tuberculosis. The main reason (96%, n = 2399) for compounding was the unavailability of age-appropriate formulations. Medicines were almost all compounded using simple syrup, vitamin C or vitamin B syrups as suspending vehicles. Final products were all oral liquids. Comprehensive stability testing was not reported for the products. Almost all of the commonly compounded medicines were found to be commercially available in dosage forms suitable for use in children in the selected countries. These medicines were all listed in the World Health Organization Essential Medicines List for children as well as in the current edition of the Essential Medicines List of Nigeria. The fact that they were compounded highlights the need for improved access to age-appropriate dosage forms for children in Nigeria. The study recommends policy expansion through a three-pronged approach to improving access: increased supply through facilitated importation/accelerated product registration, or in-country manufacturing; rational drug use including therapeutic substitution, and establishment of a national formulary for compounding.